Which was proposed as a corollary to Billingham’s criteria. Meanwhile, this provided chances to modulate GvHD by controlling lymphocyte trafficking. Mesenchymal stromal cells are multipotent non-hematopoietic progenitor cells of stromal origin that can be isolated from the bone marrow or other tissues. MSCs have potent immunomodulatory effects. When cultivated with dendritic cells, T-lymphocytes and NK cells, they can shift them to the anti-inflammatory phenotypes. Some soluble factors participate in this processes, such as IL10, nitric oxide, indoleamine 2,3-dioxygenase, prostaglandin E2, etc. Therefore, MSCs have been employed to treat various immune disorders in animal models and clinical settings. SLOs, including spleen, lymphoid nodes, mesenteric lymphoid nodes, Peyer’s Patches, etc, are‘hubs’of immune surveillance. Our previous study showed that CCR7 guide the migration of MSCs to SLOs, separate GvHD from GvL effect. In this study, we further demonstrated that the inducible immunomodulatory activity in vitro of MSCs/CCR7 is depending on the NO production. Transfused MSCs/CCR7 relocate at the appropriate T cellrich zones within SLOs and inhibit GvHD lethality through spoiling the fourth supplemental Billingham’s tenet. As the clinical GvHD-therapy result of MSCs is not as satisfactory as expected in multicenter phase III clinical studies. The aim of our present study is to further investigate the mechanism of enhanced in vivo immunomodulatory of CCR7 carrying MSCs. CCR7 can guide various types of cell to SLOs, where generate immune responses or induce tolerance. As one kind of Nutlin-3 professional APCs, DCs are the most potent initiator of in vivo immune responses. Upon maturation, DCs upregulate CCR7 expression and migrate from the peripheral tissues to the T-cell regions of SLOs, followed by instigating T-cell activation. Regulatory T cells are instrumental to induce and maintain tolerance in transplantation immune response. Moreover, Tregs mature in the SLOs of the recipients. Tregs induce allo-tolerance by interacting with APCs and T cells, which process requires their proper homing to the lymphoid tissues. CCR7 expression is important not only for Treg homing to the draining LN, but also for optimal Tregs suppressive function exerting. Since murine MSCs and human MSCs scarcely express CCR7 at the mRNA level and cell surface protein level, we introduce CCR7 gene into murine MSCs by lentivirus infection. To our excitement, CCR7 carrying MSCs can target migrate to and relocate at the appropriate T cell-rich zones within SLOs, which set a foundation for MSCs/CCR7 to shape T cell immune response in vivo. Owing to the pivotal relocation sites, MSCs/CCR7 at the same dosage displayed enhanced effect than normal MSCs in prolonging the survival and alleviating the clinical scores of GvHD mice. T lymphocytes are classified into four different subsets. Expressing CD62L and CCR7, Na ve T and central memory T cells can home to SLOs. Activated by APCs, effector memory T and effector T cells lose the expression of CD62L and CCR7, emigrate from SLOs into the peripheral inflammatory tissues.